Ys. Jin et al., ALTERED DNA RECOGNITION AND BENDING BY INSERTIONS IN THE ALPHA-2 TAILOF THE YEAST A1 ALPHA-2 HOMEODOMAIN HETERODIMER/, Science, 270(5234), 1995, pp. 290-293
The yeast MAT alpha 2 and MATa1 homeodomain proteins bind cooperativel
y as a heterodimer to sites upstream of haploid-specific genes, repres
sing their transcription. In the crystal structure of alpha 2 and a1 b
ound to DNA, each homeodomain makes independent base-specific contacts
with the DNA and the two proteins contact each other through an exten
ded tail region of alpha 2 that tethers the two homeodomains to one an
other. Because this extended region may be flexible, the ability of th
e heterodimer to discriminate among DNA sites with altered spacing bet
ween alpha 2 and a1 binding sites was examined. Spacing between the ha
lf sites was critical for specific DNA binding and transcriptional rep
ression by the complex. However, amino acid insertions in the tail reg
ion of alpha 2 suppressed the effect of altering an a1/alpha 2 site by
increasing the spacing between the half sites. Insertions in the tail
also decreased DNA bending by a1/alpha 2. Thus tethering the two home
odomains contributes to DNA bending by a1/alpha 2, but the precise nat
ure of the resulting bend is not essential for repression.